Anticariogenic compositions and methods



United States Patent Office 3,532,787 Patented Oct. 6, 1970 3,532,787 ANTICARIOGENIC COMPOSITIONS AND METHODS Joseph C. Muhler, Indianapolis, Ind., assignor to Indiana University Foundation, Bloomington, Ind., a corporation of Indiana No Drawing. Original application May 3, 1966, Ser. No. 547,188, now Patent No. 3,441,371. Divided and this application Dec. 4, 1968, Ser. No. 798,238 The porfiou of the term of the patent subsequent to June 21, 1983, has been disclaimed Int. Cl. A61k 7/16 U.S. Cl. 42452 20 Claims ABSTRACT OF THE DISCLOSURE New compositions of matter, namely, zirconium hexafluorogermanate [Zr(GeF and Zirconyl hexafluorogermanate [ZrOGeF have been discovered. These compounds, when incorporated in oral compositions for dental caries prophylaxis (e.g., as constituents of a dentifrice, prophylaxis paste, or mouthwash), have demonstrated substantial utility as anticariogenic agents.

This application is a division of applicants copending application for U.S. Pat. Ser. No. 547,188, filed May 3, 1966, now U.S. Pat. No. 3,441,371.

This invention relates to new compositions of matter, and more particularly to salts comprising zirconium, germanium, and fluoride ions and to uses thereof astopical- 1y effective anticariogenic agents.

It is commonly recognized that the presence of small amounts of fluoride in drinking water (e.g., 1.0 microgram fluoride per milliliter) has a pronounced effect in reducing the incidence of dental caries in permanent teeth of children consuming such Water from birth through eight years of age. Soluble fluoride salts have been introduced into public water supplies in a number of communities with good result. This medium for providing fluoride is not feasible, however, where drinking water is obtained from small, private fluoride-deficient sources such as individual wells, etc., rather than from fluoridated (naturally or fortified) common public sources. Further, the addition of fluoride to common public water sources is not always accepted or permitted nor is it completely effective. Moreover, much benefit is derived from the use of topical anticariogenic materials even in fluoridated areas.

Topical application of aqueous fluoride solutions by dentists or dental hygienists provides an excellent measure of protection against caries. Various fluoride compounds have been employed in this manner, including sodium fluoride, stannous fluoride, and stannous fluorozirconate (SIIZI'FE), which is the subject of applicants copending United States patent application, Stannous Fluorozirconate and Composition for Caries Prophylaxis Containing Same, Ser. No. 291,173, filed June 27, 1963, now U.S. Pat. No. 3,266,867. Another method of utilizing the anticariogenic properties of fluoride salts comprises incorporating such fluoride salts with a compatible abrasive (such as lava pumice or zirconium silicate) to form a prophylactic paste composition for use by dentists or dental hygienists in periodic cleaning and polishing of the teeth, as set forth and described in applicants copending United States patent application, Prophylactic Dental Paste Compositions Comprising Zirconium Silicate, Ser. No. 314,602, filed Oct. 8, 1963, now U.S. Pat. No. 3,257,282.

Limitations on the availability and eflectiveness of fluoride prophylaxis by way of water supplies have also led to extensive efforts to incorporate various fluoride salts in oral compositions such as dentifrices, mouthwashes, and the like for use in the home. Again, various fluoride compounds have been employed in this manner, especially stannous fluoride.

Although effective caries protection has been obtained through the use of the aforementioned fluoride compounds in compositions adapted for topical application to teeth, occasional side effects have been experienced with certain of the known anticariogenic agents, particularly certain tin-containing salts. For this reason, dental researchers have continued their efforts to find new compositions which are not only anticariogenically more effective, but which also reduce undesirable side effects.

Accordingly, it is a primary object of the present invention to provide new anticariogenic compounds comprised of zirconium, germanium, and fluorine which exhibit a high level of anticariogenic effectiveness and which are relatively non-toxic to living organisms.

It is a related object of the present invention to provide compositions which contain the said anticariogenic compounds and which are adapted for topical use in preventive dentistry.

A further object is to provide anticariogenic compounds of the character described which can be used at very high concentrations relative to known anticariogenic fluoride-containing compounds.

Yet another object of the present invention is to provide an improved method of reducing the solubility of dental enamel which comprises the topical application thereto of compositions containing the said anticariogenic compounds.

These and other objects, advantages, and features of the subject invention will hereinafter appear, and, for purposes of illustration, but not of limitation, various exemplary embodiments of the subject invention are hereinafter described in detail.

In accordance with the subject invention, new salts comprising zirconium, germanium, and fluoride ions have been discovered specifically, these salts are zirconium hexafluorogermanate [Zr(GeF and Zirconyl hexafluorogerrnanate [ZrOGeF It has been further found that these new compounds are highly effective as anticariogenic agents when utilized topically (i.e., in local applications to the teeth) either alone or in combination with other materials, as hereinafter described.

PREPARATION AND PROPERTIES 4.181 g. (0.025 mole) of anhydrous ZrF and 5.23 g. (0.05 mole) of GeO were dissolved in 25.392 ml. of 50 percent aqueous hydrofluoric HF solution, and the Zr(GeF crystals were collected in accordance with the method above indicated. Zr(GeF synthesized in this manner was obtained in an 88 percent yield. Theoretical and actual chemical analyses of this product conformed to the values reported in Table I.

TABLE I-ANALYSES Percent Element Theoretical Actual Fluorine 49. 09 49. 0 Germanium 31. 27 31. 3 Zirconium 19. 64 19. 7

Zirconyl hexafluorogermanate [ZrOGeF is a graywhite crystalline compound which melts at a temperature in excess of 310 C. and which has a refractive index of 1.558. ZrOGeF can be prepared in the following manner. One mole of Ge and two moles of potassium fluoride [KF] are dissolved in an excess of 50 percent HF solution. The resulting solution is neutralized with 50 percent potassium hydroxide [KOH], thereby precipitating potassium hexafluorogermanate [K GeF which is collected. An equimolar mixture of K GeF and zirconium oxychloride [ZrOCl is dissolved in a minimal amount of water, and the resulting solution evaporated. The precipitate, which is ZrOGeF is collected and dried.

EXAMPLE II 5.230 g. (0.050 mole) of GeO and 2.905 g. (0.05

urements obtained from a film record when each of the Zirconiurn-germanium-fluoride salts was treated as described, and for comparative purposes corresponding values obtained with ZrF GeO (hexagonal); GeO (tetragonal); and ZrOCl have also been included. The values under d are the interplanar distances expressed in Angstroms, and the values given under I represent the relative intensities of the lines obtained by arbitrarily assigning a value of 100 to the most intense line. The data presented in Table III show that the X-ray diffraction pattern for the novel zirconium-germanium-fluoride salts herein disclosed are distinctive and are readily distinguishable from the patterns of the other materials evaluated and from the patterns of each other.

TABLE III.XRAY DIFFRAOTION DATA a! I d I d I (l I d I d I d I 1 Evaluated by paper trace-X-ray diffraction procedure.

TAB LE II.ANALYSE S Percent Element Theoretical Actual 38. 8O 38. 7 24. 71 24. 8 5. 45 5. 5 Zirconium 31. 05 31. 0

The presently disclosed zirconium-germanium-fluoride salts have each been characterized according to the conventional Hull-Debye-Scherrer X-ray diffraction powder technique in order to produce a film record. Exposure was made using a standard X-ray diffraction camera (diameter 114.6 mm.) for 4.0 hours at 35 kv. and 18 ma. with a copper target and a nickel filter. As is known to one skilled in the art, this technique causes all chemical compounds to refract X-rays according to a pattern specific for each compound. The X-rays expose a film according to a specific pattern, which appears on the film as characteristic lines, the inter-planar spacing of which and the relative intensity of which may be measured in order to identify the compound. Table III records meas- AN TICARIO GENIC EFFECTIVENESS The anticariogenic eifectiveness of the zirconium-germanium-fluoride salts may be demonstrated by the dental caries experience of rate (standard experimental animals for anticariogenic studies). The elfect of various compositions in reducing the solubility of dental enamel in acid is a reliable indicator of anticariogenicity. Enamel solubility characteristics of dental compositions can be determined by a number of tests well known in the art. The particular test for reduction in tooth enamel solubility described herein comprises a comparison of acid solubility of a given tooth before and after treatment with a given test composition. The said comparison is expressed as ESR, that is, enamel solubility reduction.

Rat tooth ESR is determined in vivo as follows. The teeth of a group of suitably selected test rats are given single one-minute topical applications with solutions of various fluorides, and the animals are sacrificed twenty minutes thereafter. Each mandibular hemijaw is removed and the clinical crowns of each are decalcified in 0.2 N (pH 4) sodium acetate buffer for twenty minutes, and the decalcification solutions are analysed for phosphorus by a colorimetric method (Fisk and Subbarow, The Colorimetric Determination of Phosphorus, Journal of Biological Chemistry, 66: 375, 1925). Phosphorus liberation of the teeth topically treated with the various fluoride solutions is compared with that of teeth similarly treated with nonfiuoride containing control solutions, and the result of such comparison is reported as a percentage reduction of enamel solubility (i.e., ESR).

Table IV reports percentage reduction values achieved in the rat tooth ESR test with topically applied aqueous solutions of the zirconium-germanium-fluoride salts of the present invention at a 1000 PPM fluoride ion level.

5 The high level of anticariogenic activity of the new compounds is clearly evidenced by the percentage reduction values shown below.

TABLE IV ESR, mean pH of percent; Compound solution reduction Zl(GeF5)z 2. 3 70. 06 ZrO GeFa 1. 5 70.83

Percentage reduction values for topically applied aqueous solutions or slurries of Zr(GeF and ZrOGeF at various levels of concentration are shown in Table V. High levels of anticariogenic effectiveness were obtained at all levels tested.

TABLE V ES R, mean percent reduction Percent conc.

Fluoride compound Z1(G8Fs)2 ZrO GeFe Table VI-VIII report comparative ESR data achieved with the new zirconium-germanium-fiuoride salts and several known fluoride-containing anticariogenic agents. In the studies reported in Table VI, the aqueous test solutions were prepared so that each was equivalent (on a fluoride ion basis) to an 8 percent SnF solution. Likewise, in Table VII the aqueous solutions or slurries were all equivalent to a 24 percent SnF solution, and in Table VIII the solutions or slurries were all equivalent to a 24 percent SnZrF solution. In all cases the new zirconium-germanium-fluoride salts were at least as effective as the tested known anticariogenic compounds.

TABLE VI ESR, mean Percent percent Fluoride Compound cone. pH (natl) reduction 8. 2. 6 24.2 SnFZ 4.29 6. 9 16. 3 3. 95 1. 4 81. 5 5. 00 1. 5 81. 6 5. 51 2. 1 26. 5

TABLE VII ESR, mean Percent percent Fluoride Compound cone. pH (natl) reduction 24. 00 2. 3 46. 7 12. 86 6. 7 30. 3 11. 86 1. 0 93. 1 15.00 1. 7 84. 3 SnZrFs 16. 54 1. 7 81. 4

TABLE VIII ESR, mean. Percent percent Fluoride Compound cone. pH (natl) reduction 24. O0 1. 5 76. 3 snZrFfi 17. 20 1. 0 97, 5 21. 68 1. 2 90.7 34. 83 2.1 58.8 18. 67 6. 6 51. 5

data illustrating duration of effecaqueous solution. Animals in the first subgroup were sacrificed twenty minutes after receiving the initial topical treatment. The other subgroups were sacrificed at the following intervals of time: two and one-half days; five days; and ten days. The topical solutions were equalized to the fluoride content of 8 percent Zr(GeF The hemijaws were prepared and the enamel solubilities determined as hereinbefore described. It a minimum desired reduction level of 50 percent is selected, the zirconiumgermanium-fluorides would require reapplication only half as often as SnF or SnZrF TABLE IX ESR, mean percent reduction Fluoride Percent Compound cone 20 min. 2% days 5 days 10 days TABLE X Conc., percent Fluoride compound Length of topical ESR Zr(GeFs) 2 Z1(GeFa) 2. Z1( GeFs 2 Zr(GeFs)2 Z1( GeFu)2 ZrO GeFe. ZrO GeFs.

ZrO GeFt..- ZrOGeFa-.. ZrO GeFa The new zirconium-germanium-fluoride salts of the present invention also have outstanding utility as anticariogenic constituents of oral composition for caries prophylaxis. In general, such compositions (which include topical solutions, prophylactic paste compositions, and dentifrice preparations) will contain from about 0.1 to about 50% of the zirconium-germanium-fluoride salts of the present invention. Oral compositions which are designed for relatively frequent use in the home (e.g., dentifrice and mouthwash preparations) typically contain lower levels of the salts of the present invention than do the prophylactic pastes or topical solutions. Dentrifrice preparations preferably comprise from about 0.1 to about 0.5% zirconium-germanium-fluoride salts. Prophylactic paste compositions preferably comprise about 10 to 30% of the zirconium-germanium-fluoride salts of the present invention. Topical solutions incorporating the Zirconiumgermanium-fluoride salts of the present invention preferably comprise about 0.1 to about 50% of the salt, and preferably about 40 to 20% of the salts.

Dentifrice compositions containing the zirconium-germanium-fluoride salts constitute a preferred embodiment of this invention and may contain the usual dentifrice components, but preferably, ionically compatible adjuvants are used. For example, resinous abrasive materials including particulate condensation products of melamine and urea or formaldehyde and the like which do not form insoluble salts with fluoride ion or inactivate zirconium, germanium, and fluoride ions by adsorption can be used to advantage. Other abrasives which have proven practical in fluoride containing dentrifrice compositions and which can be used herein include zirconium silicate, calcium pyrophosphate, insoluble metaphosphates and alumina. Mixtures of these abrasives can also be used.

The total amount of abrasive material in dentifrices of this invention can range from 0.5% to by weight of the total composition. Preferably, toothpastes contain from 20% to 60% by weight and toothpowders contain from 60% to 95% by weight.

Toothpastes require a binder substance to impart desired texture properties. Natural gum binders such as gum tragacanth, gum karaya, gum arabic, etc. and seaweed derivatives such as Irish moss and alginates, and water soluble cellulose derivatives, such as hydroxyethyl-cellulose and sodium carboxymethyl cellulose can be used for this purpose. Desirably those materials are employed which are most compatible with fluoride ion. Binders which have no ionic groups, such as hydroxyethyl cellulose are especially preferred. Improvements in texture can also be attained by including an additional material such as colloidal magnesium aluminum silicate.

Thickening agents in an amount of from 0.5% to 5.0% by weight can be used to form a satisfactory toothpaste.

Toothpastes conventionally contain sudsing agents. Suitable sudsing agents include, but are not limited to, watersoluble alkyl sulfates having from 8 to 18 carbon atoms in the alkyl radical, such as sodium lauryl sulfate, watersoluble salts of sulfonated monoglycerides of fatty acids having from 10 to 18 carbon atoms in the alkyl radical such as sodium coconut monoglyceride sulfonate, salts of fatty acid amides of taurines such as sodium-N-methyl palmitoyl tauride, and salts of fatty acid esters of isethionic acid.

Sudsing agents can be used in the compositions of this invention in an amount of from about 0.5% to about 5.0% by Weight of the total composition.

It is also desirable to include some humectant material in a toothpaste to keep it from hardening. Materials commonly used for this purpose include glycerine, sorbitol equal groups, and the teeth of each rat were brushed five times within a three-hour period with a sample dentifrice preparation. The rats were sacrificed thereafter, and ESR data was obtained in the previously described manner. The results of these tests are given in Table XI. The sample dentifrices utilized as the anticariogenic active component mixtures of a fluoride-containing salt and an active-phosphate compound, for example, an ammonium salt of a condensation product of NH and P commercially available under the tradename Victamide from Victor Chemical Company, in the manner set forth and described in applicants copending United States patent application, Dentifrice Prep aration, Ser. No. 402,920, filed Oct. 9, 1964, now aban' doned. As their cleaning and polishing components, the dentifrices utilized a critically defined zirconium silicate [ZrSiO in accordance with applicants copending United States patent application, Anticariogenic and Anti-Calculus Dentifrice Cleaning and Polishing Agent and Dentifrice Preparations Incorporating Same, Ser. No. 453,515, filed May 5, 1965, now abandoned.

The data reported in Table XI verify the high level of anticariogenicity obtained with dentifrice preparations embodying the zirconium-germanium-fluoride salts of the present invention.

TABLE XL-ANTIOARIOGENIO EFFECTIVENESS OF ZIROCONIUM-GERMANIUM-FLUORIDE SALTS Constituents, parts byWeight Sorbitol, Group No. ZrSiO; ZrO GeFu Z1(G8Fs)2 Victamide Water Glycerin 70% aqueous Sudsers Binders 1 (Control.

Constituents, Parts byWeight E.S.R. Data Brushing N o. of Mean per- M-HPO H PO4 Zr(PO3) ZrP2O Zla(PO4)4 KHCaHtOi pH teeth cent red and other polyhydric alcohols. The humectants can comprise up to of the toothpaste composition.

Flavoring materials may be included in toothpaste formulations including small amounts of oils of Wintergreen and peppermint and sweetening agents such as saccharine, dextrose and levulose.

The efiicacy of toothpaste compositions in accordance with this invention can be seen from the following studies.

When incorporated in dentifrice preparations, the novel zirconium-germanium-fluoride salts of the present invention are comparable in effectiveness to other known anticariogenic agents (such as, for example, SnF Table XII records rat ESR data obtained in a brushing study, carried out according to the previously described procedure in which dentifrices comprising SnF and Victamide are utilized. The data of Table XII verify the high level of anticariogenic eifectiveness of dentifrice prep- A suitable number of rats were divided into thirteen 7 arations embodying the salts of the present invention.

TABLE XIL-ANTICARIOGENIC EFFECTIVENESS OF VARIOUS FLUORIDE CONTAINING DENTIFRICE PREPARATIONS Constituents, Parts byWeight ESR Data Sorbi- No. Mean Vict- Glycto], 70% Suds- Bind- Brushof percent ZrSiOi SnFz ZrOGeF amide Water erin aqueous ers ers M-HPO; H3PO4 Sn2P2O7 KHCsHAOi mg pI-I teeth red.

The following examples provide exemplary dentifrice tained with prophylactic paste compositions embodying formulations comprising the zirconium-germanium-fluothe salts of the present lnvention. ride salts of the present invention. 15 TABLE XIII EXAMPLE III Prophylactic Paste Constituents ESR data,

. mean A toothpaste composition is prepared by conventional (Per- 4 (Per- Water percent methods having the following composition: Polishing Agent cent) Fluoride cent) (percent) leductlon L .0 Percent y welglt gigiitgif i ifiwzrogegnu 2. 8 65.6 r i 7. ZrO e 8. 16,0 87.4 Zirconium liqxafiuorogermanate 2 ZrSiO: 34.0 Zr(GeF 2 0 14,0 0,2 ZlIcOnlHm slllcate g-g %lgl84 gn o rmfl 38.8 r 1 4 n r 0.

g g t g; u 1 g Lava pumice.-." 61.1 SnFz 8.9 30.0 66.8 f f '1". The anticariogenic effectiveness of the novel zirconi- E P (7 aqueous utfim) um-germanium-fiuoride salts has also been verified in so coconut lilonog ycen e (mate human clinical studies. A total of approximately 150 sodlum lauryl ate 1 children between the ages of 6-15 years Were divided in veesum (magnesmm a ummlum mate) 5 accordance with past dental caries experience into three Sodmm carboxymetllyl ceuu ose balanced groups. Each member of each group received -p p q g 2- 8 a thorough dental prophylaxis before the clinical study Potasslflm acld P thalate g was begun. Each member of each group received treatm agents 0 :ment with a topical solution and was examined after six (Worm? agents 108 W months. The children in Group I received an 8% solu- Sacchann tion of Zr(GeF Group II received a 12.6% solution of ZrOGeF and Group III received a 0.9% NaCl solu- 10O-00 tion. The increments in the number of decayed, missing,

When diluted with Water and brushed upon the teeth and filled teeth DM and the m ts in the in the conventional manner, this composition yields sub- 40 number of y missing, and filled sul'faces E tantial r d tion i a i i id were recorded. The percentage reduction in caries 111 cidence was established by comparison with the control EXAMPLE IV group (Group III). The results of this study are pre- Another toothpaste composition is prepared as in EX- sented in Table XIV.

TABLE XIV.HUMAN CLINICAL STUDIES Percent Red. No. of Fluoride Conc., Group subjects compound percent DMFI DMFS Teeth Surfaces Zl(G9F6)2 8.0 0.40 1.20 76.8 58.4 49 ZIOGGFB--- 12.6 0.43 0.63 75.9 78.2 43 Control 1. 72 2.89

ample III, but containing zirconyl hexafluorogermanate The results of the human clinical studies, as reported in in place of zirconium hexafluorogermanate. This compo- Table XIV, clearly establish the anticariogenic effectivesition provides an effective means for caries prophylaxis ness of the zirconium-germanium-fluorides of the present when used in the conventional manner. invention.

The new zirconium-germanium-fiuoride compounds are As previously noted, the new zirconium-germaniumuseful as anticariogenic constituents when incorporated fluoride salts of the present invention are especially usei a l i d li hi agent l pumice ful when incorporated in oral compositions for caries or zirconium silicate) to form a prophylactic paste P p y adapted for application once or twice a year by a dentist ANIMAL TOXICITY of dental hygienist Preferred Prophylactic pastes In addition to exhibiting a high level of anticariogenic bodyil'lg Zirconium Silicate are Set forth and described effectiveness, the zirconiumgermanium-fluoride salts of in lp Copending United States Patfllt application the present invention are of low toxicity comparing quite entitled Prophylactic Dental Paste Compositions Comfavorably in this regard with other anticariogenic fluo- Prising Zirconium Silicate, 314,602, filed rides, as shown by the following experimental studies.

8, 1963, now Pat. No. 3,257,282. Table XIII contains The toxicity of the zirconiumgermanium-fluoride salts representative ESR results obtained through the use of has been determined in mice (standard experimental anivarious prophylactic paste compositions. A suitable nummals for this purpose), and acute toxicity data are shown her of test rats were divided into groups and each group in Table XV, with corresponding values for NaF included was given a 15-second prophylaxis with one of the comfor comparative purposes. The toxicity is expressed in positions. Twenty minutes following treatment, the aniterms of an LD which is the lethal dose for 50% of mals were sacrificed, and enamel solubilities were dethe animals treated. The LD is expressed both in millitermined in the usual manner. The data of Table XIII grams of fluoride per kilogram of body weight and in illustrate the high level of anticariogenic effectiveness obmilligrams of compound per kilogram of body weight.

1 1 The data reveals that the test mice could tolerate significantly greater amounts of exemplary zirconium-germanium-fluoride salts than of sodium fluoride.

TABLE XV.-AC UTE TOXICITY Rat studies further reveal that zirconium-germaniumfluoride salts, when topically applied, do not damage the gingival tissue of the test animals. Groups of weaning rats were given topical applications of various fluoride compounds, and the gingival tissues were examined after 24 hours. The results indicate that the exemplary zirconium-germanium-fluoride salts are comparable or superior to known fluorides (e.g., NaF', SnF or SnZrF The particular zirconium-germanium-fluoride salts set forth and described hereinbefore are believed to be representative of a class of theoretically obtainable zirconiumgermanium-fluoride salts. Thus, it is believed that other zirconium-germanium-fluoride salts may be prepared and such other salts would be expected to exhibit the same anticariogenic utility as the specific salts disclosed herein.

While the present invention has been described herein with reference to certain exemplary embodiments thereof, it should be understood that various changes, modifications, and alterations may be effected in the materials utilized, in the proportions of materials, and in the manners of formulation without departing from the spirit and the scope of the present invention, as defined in the appended claims.

What is claimed is:

1. An anticariogenic oral composition comprising from about 0.1 to 50% by weight of zirconium hexafluorogermanate, Zr(GeF 2. An oral composition, as claimed in claim 1, and adapted for use as a dentifrice preparation, wherein the member is present at a level of about 0.1 to 0.5

3. A dentifrice preparation, as claimed in claim 1, and, further comprising about 2070% of a fluoride compatible cleaning and polishing agent.

4. An oral composition, as claimed in claim 1, and adapted for use as a prophylactic paste, wherein the member is present at a level of about 10-30%.

5. An oral composition, as claimed in claim 4, and further comprising about 30-80% of a fluoride compatible cleaning and polishing agent.

6. An oral composition, as claimed in claim 1, and adapted for direct topical application to the teeth in 12 aqueous form, wherein the member is present at a level of about 0.1-50%.

7. A method for increasing the dental caries resistance of teeth comprising the application thereto of an oral composition as claimed in claim 1.

8. A method, as claimed in claim 7, wherein the composition is a prophylactic paste comprising about 10- 30% of said member.

9. A method, as claimed in claim 7, wherein the composition is a dentifrice preparation comprising about 0.1- 05% of said member.

10. A method, as claimed in claim 7, wherein the composition is an aqueous solution comprising about 4- 20% of said member.

11. An anticariogenic oral composition comprising from about 0.1 to 50% by weight zirconyl hexafiuorogermanate, ZrOGeF 12. An oral composition, as claimed in claim 11, and adapted for use as a dentifrice preparation, wherein the ZrOGeF is present at a level of about 0.1 to 0.5%.

13. A dentifrice preparation, as claimed in claim 12, and further comprising about 20-70% of a fluoride compatible cleaning and polishing agent.

14. An oral composition, as claimed in claim 11, and adapted for use as a prophylactic paste, wherein the member is present at a level of about 1030%.

15. An oral composition, as claimed in claim 14, and further comprising about 30-80% of a fluoride compatible cleaning and polishing agent.

16. An oral composition, as claimed in claim 11, and adapted for direct topical application to the teeth in aqueous form, wherein the ZrOGeF is present at a level of about 0.1 to 50%.

17. A method for increasing the dental caries resistance of teeth comprising the application thereto of n oral composition as claimed in claim 11.

18. A method, as claimed in claim 17, wherein the composition is a prophylactic paste comprising about 1030% ZrOGeF 19. A method, as claimed in claim 17, wherein the composition is a dentifrice preparation comprising about 0.1-0.5% ZrOGeF 20. A method, as claimed in claim 17, wherein the composition is an aqueous solution comprising about 4-20% ZrOGeF References Cited UNITED STATES PATENTS 3,257,282 6/1966 Muhler 424-52 RICHARD L. HUFF, Primary Examiner 

